More on Niagen

(1 year later) Nad+ is the goal, NMN is 1step away, avoids NAMPT bottleneck, Niagen is two steps away - A form of Vitamin B3. But NMN is 1.5 times more expensive.

http://aaqg-arunarya.blogspot.in/2017/08/more-on-niagen.html why this link?

This is a patent protected nutraceutical, all its commercial forms are derived from chromadex niagen, and hence quality difference is from additional chemicals and interactions.

Niagen boosts NAD+. What's that?

xidative stress and decreased DNA damage repair in vertebrates increase with age also due to lowered cellular NAD+. NAD+ depletion may play a major role in the aging process at the cellular level by limiting (1) energy production, (2) DNA repair, and (3) genomic signaling. In this study, we hypothesize that it is not NAD+ as a cofactor in redox reactions and coenzyme in metabolic processes that has the ultimate role in aging, but rather the role of NAD+ in cellular signaling when used as substrate for sirtuins (SIRT1-7 in mammals) and PARPs [Poly(ADP-ribose) polymerases]. Both sirtuins and PARPs influence many transcription factors and can affect gene expression. As a signaling molecule, NAD+ is consumed in the reaction donating ADP-ribose and releasing nicotinamide (NAM) as a by-product. It seems that aging at the cellular level is associated with a decline of NAD+ and that NAD+ restoration can reverse phenotypes of aging by inducing cellular repair and stress resistance. Adequate intracellular NAD+ concentrations may be an important longevity assurance factor, while lowered cellular NAD+ concentration may negatively influence the life span.

What is the state of niagen as per FDA?

This 2015 determination is validated just a few days ago.

Why should anyone believe Niagen?

1.     Ultimate proof is empirical, a Japanese study started in 2016, how will anyone prove anti-aging?

2.     Cells have NaDH – NAD+ cycle. One can show empirically that NAD+ level FALL directly vary with age and tiredness correlated with age.

3.     Eating Niagen provably boosts the level of NAD+ by empirical standard measures.

4.     Anecdotally, consumers feel better. A dosage level of 250 mg has been set by informal studies (larger doses do not raise NAD+ SIGNIFICANTLY before fall to 250 mg level).

5.     It is very expensive, far more than coQ10. Cheapest reliable I could find was at amazon,  at Rs. 6913 (when link taken) per month! It is not likely to fall. I see a battle-royal on drug patents by 2020!

Some more references?

1.    Reversing Aging: Not as Crazy as You Think. TIME, 2013 Dec 19

What makes cells age? Wear and tear, yes. But biologically, says, Dr. David Sinclair, professor of genetics at Harvard Medical School, it’s lack of oxygen that signals cells that it’s their time to go. Without oxygen, the energy engines known as the mitochondria become less efficient at turning physiological fuel like glucose into the energy that the cells need to function. Eventually, they shut down…

2.  Niagen Nicotinamide Riboside New NDI Status from FDA

ChromaDex Lead Ingredient NIAGEN® Nicotinamide Riboside Receives New Dietary Ingredient (NDI) Status From the FDA

November 16, 2015

IRVINE, Calif., Nov. 16, 2015 (GLOBE NEWSWIRE) -- ChromaDex Corp. (OTCQX:CDXC), an innovator of proprietary health, wellness and nutritional ingredients that creates science-based solutions for dietary supplement, food and beverage, skin care, sports nutrition, and pharmaceutical products announced today it has received New Dietary Ingredient (NDI) status from the FDA for its patented and proprietary lead ingredient, NIAGEN^® nicotinamide riboside….

3.    Dose-Dependent Elevation of the Blood NAD+ Metabolome by NR

Dose-Dependent Elevation of the Blood NAD Metabolome by NR in Healthy Human Beings: Clinical Efficacy and Novel Diagnostic Biomarkers Abstract Nicotinamide riboside chloride (NR) is in wide use as an orally available NAD precursor vitamin. Here we conducted three experiments to determine the time and dose-dependent effects of NR on blood and liver NAD metabolomes in people and in mice, respectively. We report that human blood cell NAD+ can rise as much as 2.7-fold with a single dose of NR, that NR elevates mouse hepatic NAD+ with distinct and superior kinetics to those of Charles Brenner1 , Samuel AJ Trammell1 , Mark S Schmidt1 , Benjamin J Weidemann1 , Philip Redpath2 , Marie E Migaud2 , Frank Jaksch3 & Ryan W Dellinger3 University of Iowa, USA1; Queens University Belfast, Northern Ireland2 and ChromaDex, Inc, USA3 NAD+ Biosynthesis Study Design Phase: Day: -14 1 2 8 9 15 16 Visit: 1 2 3 4 5 6 7 2 Weeks Screening Treatment Period (3 Weeks) 7 Day Washout 7 Day Washout NAD metabolites undergo circadian oscillation(2,3). To eliminate circadian oscillation as an experimental confounder, we developed an oral gavage protocol in which male C57BL/6 mice were given single oral doses of NR at 185 mg/kg 20’, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr and 12 hr prior to sacrifice, which was always performed at ~ 2 pm. In addition, mice were dosed with equimole amounts of NA, Nam and a control saline solution, and mice were sacrificed at 2 pm without gavage.

supplementationJ Neurosci. 2006 Aug 16;26(33):8484-91 (click to download)

4.   

Nature. 2004;429:771–776. doi: 10.1038/nature02583

Calorie restriction extends lifespan in organisms ranging from yeast to mammals¹. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction². Here we show that the mammalian SIR2orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-γ (peroxisome proliferator-activated receptor-γ), including genes mediating fat storage. Sirt1 represses PPAR-γ by docking with its cofactors NCoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors). Mobilization of fatty acids from white adipocytes upon fasting is compromised in Sirt1^+/− mice. Repression of PPAR-γ by Sirt1 is also evident in 3T3-L1 adipocytes, where overexpression of Sirt1 attenuates adipogenesis, and RNA interference of Sirt1 enhances it. In differentiated fat cells, upregulation of Sirt1 triggers lipolysis and loss of fat. As a reduction in fat is sufficient to extend murine lifespan³, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals.​

5.    Rejuvenation Res. 2016 Mar 16. DOI: 10.1089/rej.2015.1767

Oxidative stress and decreased DNA damage repair in vertebrates increase with age also due to lowered cellular NAD+. NAD+ depletion may play a major role in the aging process at the cellular level by limiting (1) energy production, (2) DNA repair, and (3) genomic signaling. In this study, we hypothesize that it is not NAD+ as a cofactor in redox reactions and coenzyme in metabolic processes that has the ultimate role in aging, but rather the role of NAD+ in cellular signaling when used as substrate for sirtuins (SIRT1-7 in mammals) and PARPs [Poly(ADP-ribose) polymerases]. Both sirtuins and PARPs influence many transcription factors and can affect gene expression. As a signaling molecule, NAD+ is consumed in the reaction donating ADP-ribose and releasing nicotinamide (NAM) as a by-product. It seems that aging at the cellular level is associated with a decline of NAD+ and that NAD+ restoration can reverse phenotypes of aging by inducing cellular repair and stress resistance. Adequate intracellular NAD+ concentrations may be an important longevity assurance factor, while lowered cellular NAD+ concentration may negatively influence the life span.